We transplanted rhesus monkey endometrium into SCID mice. Our goal was to provide a new model system for study of the primate endometrium. Endometrium from spayed monkeys treated with estradiol (E2) for 14 days and then E2 + progesterone (P) for 7-8 days, was grafted subcutaneously into spayed SCID mice treated with E2 and P. Three trials were conducted to achieve mouse E2 and P levels that were in the normal range for monkeys (e.g. 244 pg E2 and 14.5 q 1.3 ng P). After 3-4 weeks of E2 + P, the grafts were sampled, and P implants removed. Grafts were collected after 2, 3, 4, 10 and 14 days of E2 treatment. P implants were replaced and remaining grafts collected after 14 days of E2 + P. Graft acceptance for basalis was excellent (89 q 4%; n=53), but grafts of functionalis were unsuccessful (0%; n=18). Established grafts contained an hypertrophied stroma and an almost complete lack of glands. Immunocytochemistry (ICC) for Ki-67 revealed abundant cell proliferation in the E2 -treated stroma. The grafts were well vascularized and some arteries were coiled. Bleeding occurred in some grafts after P withdrawal. Staining with Hoechst 32258 revealed that murine cells infiltrated the interstices of the grafts, but did not contribute to the vasculature. ICC showed strong staining for estrogen receptor (ER) and P receptor (PR) in stroma and remnant glands after E2 treatment. P treatment reduced ER staining in the remnant glands and stroma, whereas PR staining was lost only in the glands and not stroma. In summary, regulation of cell proliferation, and expression of ER and PR was similar to monkey endometrium in situ, but there was an unexpected loss of glands and hypertrophy of graft stroma under these conditions. This model provides a unique system for study of factors regulating growth of the endometrial stroma.